Guinea pigs were exposed to filtered air or liquid aerosols of either phosphate buffer or phosphate buffer containing n-formyl-methionyl-leucyl-phenylalanine (FMLP) generated with an ultrasonic nebulizer. The exposure system was designed using a feedback control technique to maintain the mass concentration of FMLP within the aerosol at 1 mg/m³ for 4 hrs. Postmortem gas trapping measurements, used as an index of airway obstruction, were not significantly altered by exposure to phosphate buffer or FMLP dissolved in phosphate buffer. In contrast, breathing rate measurements made in 10% CO₂ in air indicated that the group of animals exposed to FMLP had an increased breathing rate that peaked at 0 hrs post-exposure. Bronchoalveolar lavage measurements proved that the total number of cells harvested at 18 hrs post-exposure was significantly greater in animals exposed to FMLP than in animals exposed to filtered air or phosphate buffer. In addition, differential counts of granulocytes, lymphocytes, and red blood cells were significantly increased in animals exposed to FMLP compared to animals exposed to filtered air or phosphate buffer. The number of macrophages recovered and the resting level of superoxide released were not altered after FMLP exposure. Zymosan-stimulated macrophages from animals exposed to FMLP, however, released more superoxide than macrophages from animals exposed to either filtered air or phosphate buffer. When the guinea pig animal model response to FMLP was compared with its response to cotton dust, there were differences in terms of gas trapping and the time course of the breathing rate response in 10% CO₂ in air. The cellular responses were similar under the two exposure conditions but the magnitude of the response was greater in animals exposed to cotton dust. The results support the conclusion that FMLP contributes to the acute response of guinea pigs to cotton dust, but it is unlikely that FMLP is the only causative agent.